Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells

PLoS Genet. 2010 Apr 8;6(4):e1000898. doi: 10.1371/journal.pgen.1000898.


Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism
  • Gene Expression Regulation*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Mice
  • Mice, Knockout
  • Neurogenesis*
  • Neurons / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • Fragile X Mental Retardation Protein
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Cyclin-Dependent Kinase 4
  • Glycogen Synthase Kinase 3